Neutrophil oxygen radical generation. Synergistic responses to tumor necrosis factor and mono/polyunsaturated fatty acids
| Autor: | Anthony W. Ferrante, Alf Poulos, Yedan Li, Dianne P. Harvey |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Leukotriene B4
Neutrophils In Vitro Techniques Dinoprostone Cyclooxygenase pathway Lipoxygenase chemistry.chemical_compound Superoxides Humans chemistry.chemical_classification Inflammation Reactive oxygen species Arachidonic Acid biology Chemistry Tumor Necrosis Factor-alpha Drug Synergism General Medicine Recombinant Proteins Biochemistry Saturated fatty acid Luminescent Measurements biology.protein Fatty Acids Unsaturated Tumor necrosis factor alpha Arachidonic acid Reactive Oxygen Species Polyunsaturated fatty acid Research Article |
| Zdroj: | The Journal of clinical investigation. 97(7) |
| ISSN: | 0021-9738 |
| Popis: | In inflammatory reactions there are complex interactions of protein mediators (cytokines) and mediators derived from lipids. An important event in inflammation is superoxide production, in relation to microbicidal activity as well as tissue damage. We have studied interactions of lipid mediators with a cytokine mediator tumor necrosis factor alpha (TNF) in stimulating superoxide production by human neutrophils for this reason and because it throws light on intracellular signals activating this response. Pretreatment of neutrophils with TNF markedly augmented the amount of superoxide produced in response to AA but not to either a 20 carbon saturated fatty acid, or the hydroxy- or hydroperoxy-derivatives of AA. Not only were other polyunsaturated fatty acids (eicosapentanoic, docosahexaenoic, linolenic, linoleic acid) as effective as AA but so was the monounsaturated fatty acid, oleic acid. Indeed TNF primed the neutrophils for an increased response to a major mediator of inflammation, leukotriene B4, which is a product of AA metabolism via the lipoxygenase pathway. The data demonstrate that two major types of mediators generated during an inflammatory response have synergistic action on neutrophils in the generation of reactive oxygen species. In contrast, neutrophils primed with TNF and challenged with PGE2, a product of AA metabolism via the cyclooxygenase pathway, showed a reduced chemiluminescence response. This identifies an important interaction between unsaturated lipids and cytokines which is likely to play a critical role in disease processes and nutrient modulation of the immune responses. |
| Databáze: | OpenAIRE |
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